Effects of sterilization on an extracellular matrix scaffold: Part II. Bioactivity and matrix interaction

Abstract

Small intestinal submucosa (SIS) has been successfully used to treat a variety of damaged or diseased tissues in human patients. As a biologic scaffold, SIS stimulates repair of damaged or diseased tissues and organs with tissue that is similar in structure and function to the material it was meant to replace. To meet clinical safety requirements, biologic materials from animal tissues must undergo processing treatments to minimize host immune response and to eliminate the possibility of disease transmission. The effect of peracetic acid disinfection, lyophilization, and ethylene oxide sterilization on the in vitro bioactivity of the processed SIS was therefore examined in murine fibroblasts and pheochromocytoma (PC12) cells. Specifically, the ability of processed SIS to support fibroblast attachment, to stimulate PC12 cell differentiation, and to upregulate fibroblast VEGF secretion was examined. Fibroblasts attach to the sterilized SIS, remain viable, and more than double their secretion of VEGF as a result of interacting with the SIS matrix components. Additionally, PC12 cells exhibit increased neurite outgrowth following stimulation by SIS matrix proteins versus controls. We conclude that a biologic scaffold can be prepared for human use and still retain significant bioactivity.

Generating Elastin-Rich Small Intestinal Submucosa–Based Smooth Muscle Constructs Utilizing Exogenous Growth Factors and Cyclic Mechanical Stimulation

“…8 SIS also contains other factors such as VEGF, but VEGF is known to degrade in the processing of the matrix. 9 These growth factors and cytokines likely aid in the remodeling response that occurs following implantation of SIS; however, in vitro, the inherent growth factors in the SIS may not be adequate to promote penetration of cell types other than fibroblasts.…”

“…11 It has also been demonstrated that FGF-2 retains its bioactivity in SIS following processing. 9 The growth factors FGF-2 and VEGF simulate urothelial cell presence, 12 have been shown to increase proliferation in BSMC derived from neurogenic bladders, 13 and have an antiapoptotic effect in culture of human BSMC.…”

Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds

“…[16][17][18][19][20] There is convincing evidence that hostmediated degradation of ECM scaffolds is typically completed within 8-12 weeks and is necessary to realize the full beneficial effects of ECM-mediated tissue remodeling, [21][22][23] but the mechanisms by which such scaffold degradation occurs have been largely ignored.…”

Tissue engineering with gellan gum

“…Various techniques are in use for this purpose including autoclaving [34][35][36] , ethylene oxide treatment 37 , microfiltration 38 , and antibiotic supplements 39 . Although no studies directly compare these methods with respect to their impacts on GG, equivalent investigations using other polysaccharides [40][41][42][43] and ECM materials 40,44,45 provide a good indication of the likely effects on GG. In general, these studies report that common sterilisation procedures are generally effective at removing or deactivating contaminants without loss of the biological activity.…”